1. Field of the Invention
The present invention relates to the treatment of benign prostatic hyperplasia and/or prostate carcinoma. More particularly, the present invention relates to a process for isolating N-butylbenzenesulfonamide (NBBS) from biological material, the chemical synthesis of benzenesulfonamide derivatives, the use of NBBS and benzenesulfonamide derivatives for treating benign prostatic hyperplasia and/or prostate carcinoma, the production of medicaments for the treatment thereof, and the use of NBBS and benzenesulfonamide derivatives as a lead substance in the development of active substances for treating benign prostatic hyperplasia and/or prostate carcinoma.
2. Description of the Prior Art
Benign enlargement of the prostate, also called benign prostate syndrome (BPS) or benign prostatic hyperplasia (BPH), and prostate cancer (also known as prostate carcinoma) are among the most common diseases affecting males as they age.
About 50% of men over the age of 60 years are afflicted by a benign form of prostate enlargement.
Benign prostatic hyperplasia is closely related to the development of prostate cancer, which is the most common cancer affecting men in middle age in the western countries and the second most common cause of cancer death in men.
BPH and prostate cancer are characterized, inter alia, by the progressive enlargement of the prostate. Enlargement of the prostrate causes increasing narrowing ( i.e., obstruction) of the urethra and obstruction of the bladder outlet, leading to problems when urinating. In the advanced stage the complete obstruction of the urethra, so-called anuria, leads to an emergency that requires immediate treatment.
The growth of the prostate is controlled by the male sex hormones, the androgens.
Several methods are available for the effective treatment of prostate carcinoma, amongst others, hormone therapy. Once the cancer has disseminated, a cure of prostate cancer is no longer possible. This applies to as many as one third of the patients at the time of the first diagnosis. In these cases, suppression of tumour growth and alleviation of the accompanying complaints are at the focus of the therapy. By suppressing the production of male sex hormones (testosterone) in order to counteract the transactivation function of the androgen receptor, it is possible to achieve temporary growth inhibition.
The major aim of the current therapies is to inactivate the androgen receptor (AR). The androgen receptor regulates male sex differentiation, is responsible for male fertility and promotes the growth of the normal prostate gland, but also promotes the proliferation of cancer cells of the prostate. Therefore, the androgen receptor has become an important target for prostate carcinoma therapy.
However, the current therapies are clearly limited since a prostate carcinoma will eventually exhibit resistance to this therapy.
The AR induces the expression of AR-responsive genes when it is bound to androgens. The inactivation of the androgen receptor is achieved either by reducing androgen synthesis or by administering androgen antagonists. So far, bicalutamide, flutamide, hydroxyflutamide (OH—F), nilutamide and cyproterone acetate (CPA) are used for the treatment of prostate cancer. These substances are administered with the aim of inactivating the transactivation of human androgen receptor.
However, eventually during the therapy the prostate carcinoma starts to regrow and exhibit resistance to the hormone deficiency. It has been found that androgen receptors are present and still remain active despite the treatment. The causes underlying this phenomenon remain largely unclear.
It is, however, apparent that there is a need for novel active substances for a successful treatment of BPH and/or prostate carcinoma.
Plant extracts for treating symptoms accompanying the enlargement of the prostate are traditionally wide-spread in many countries. The most commonly used extracts are those from the African plum tree (Pygeum africanum), which is also called Prunus africana (Hook. F.) Kalkm. according to more recent nomenclature, the Saw palmetto (Serenoa repens) and the pumpkin (Cucurbita pepo). The standardised lipophilic extracts from these plants contain sterols, saturated and unsaturated fatty acids as well as n-docosanol. The exact mechanism of action is yet unknown; it has been presumed, however, that the improvement of the symptoms associated with prostate enlargement is attributable to the sterol compound β-sitosterol, which is the quantitatively predominant component contained in the extracts.
Most of the clinical studies on the efficacy of extracts from the African plum tree were performed using chloroform extracts from its bark. This chloroform extract contains, inter alia, phytosterols, short-chain unsaturated fatty acids (lauric acid, myristic acid) and long-chain unsaturated fatty acids (oleic acid, linoleic acid. It is licensed under the designation TADENAN® in Italy, France and other European states, but not in Germany, for symptomatic treatment of BPH.
The placebo-controlled short-term studies using chloroform extracts from P. africana indeed showed a moderate clinical efficacy, but their concept was not even in accordance with the minimum requirements of the International Consultations on BPH. For this reason, a clear assessment of these studies is regrettably not possible.